DE69627791T2 - Reaction device for automatic analyzes - Google Patents

Description

Background of the Invention

Field of the Invention

The present invention relates on a reaction device for the analysis of a lens substance by using a chemical Reaction or a biochemical reaction. In particular relates The present invention relates to a reaction device that is designed for automatic Immunoassay of a trace amount of a lens substance in a biological Sample placed in a vessel or container like for example a blood sampler and a sample reaction vessel such as a liquid sample such as serum and urine and a liquid extract that passes through Extraction from a tissue or the like is obtained by exploitation an immune response.

The reaction device of the present invention is related to the application in automatic analysis of a trace amount of a substance using an immune response as an example. conventional such an automatic analysis system has a reaction device (an incubator) on, at which reaction vessels, the contain a sample and reactant in contact with a surface and is brought to an environment that is at a constant temperature is held for a prescribed period of time to allow that the reaction of the sample with the reactant is satisfactory constant conditions. The system for the reaction (or incubation) includes a batch system in which the reaction vessel is for the prescribed Response time is fixed, and a conveyor system or transport system, in which the reaction can proceed, the reaction vessel passing through transported the incubator becomes.

In a process of the conveyor system Reaction tubes with one endless chain hooked up, which is in a closed loop move in contact with a temperature controlled surface, and distance by distance (Division for Division) can be moved at a predetermined time interval. at another method of the conveyor system become reaction vessels on one Rotary table arranged at a prescribed angle at a prescribed time interval is rotated. With each of the procedures serves the vascular delivery mechanism also as the incubator. In yet another method of conveyor system become reaction vessels in one temperature controlled water bath submerged.

Automatic analysis by immunoassay needed frequently a reaction time (incubation time) of one or more hours. With such a long treatment time, it is necessary that the Incubator for an efficient treatment of many reaction vessels simultaneously in one reaction state can hold. For example, it is necessary to get measurement results every 30 seconds for Series of one-hour reactions to get that at least 120 Reaction vessels at the same time be kept in a reaction state.

In addition, it is necessary that the reaction device is getting smaller. For the small design to fulfill the incubator may preferably meet the requirements set out above the reaction vessels so compact as possible hold.

For a compact setting of the reaction vessels is the batch system mentioned above more suitable, in which the reaction vessels without Movement in the incubator are fixed. However, it is with one such a batch system disadvantageously very difficult respective reaction vessels at the maintain the same temperature. More specifically, many reaction vessels cannot can be easily controlled so that they are technically all at the same temperature in an incubation room. With the batch system the temperature is forcibly distributed in the room in the incubator, to cause a fluctuation in the reaction conditions for the respective reaction vessels. Consequently the measurement accuracy is affected by the difference in position. Furthermore, in the case of a two-step process, a Intermediate washing performed by transferring of the reaction vessel to the other unit or by adding a washing device to the reaction vessel in the Incubator is brought. The mechanism for the transfer must be considered be extraordinarily precise on the positional accuracy of what technically and economically is a disadvantage.

On the other hand, the conveyor system in which the reaction can proceed with the reaction vessel being conveyed is advantageous in view of the uniformity of the reaction conditions, since all the reaction vessels are relatively easy with the same temperature hysteresis regardless of the temperature distribution in the incubator by conveying all the reaction vessels along the same route can be treated. However, the temperature of the environment should control the entire conveying area, so that the conveying system with a linear conveying route requires an extraordinarily large length of the incubator. The space efficiency can be improved in the chain conveyor method of the conveyor system mentioned above, in that the conveyor track is curved several times. However, the curved section vascular conveying mechanism requires one tooth for each curved section, which requires many parts and the conveying mechanism becomes complicated and disadvantageous in terms of cost. The rotary table method, which uses concentric multiple conveying routes, is not suitable for all reaction vessels under the same reaction conditions and the same temperature hysteresis to keep rese, whereas the turntable method, which uses a vessel structure with a conveyor circle circumference, disadvantageously requires a turntable with a large diameter.

It also requires a dual purpose reaction device for uses for a one-step process without intermediate washing and a two-step process with one intermediate washing additional Connections, which have an intermediate washing connection, a second immunoreagent distribution connection, a final wash port and an acquisition port for inspection of a marker or an article derived from a marker is in combination with the reaction device. The intermediate washing connection and the final wash port each require a vertical drive mechanism, a washing liquid supply line and a washing liquid discharge line. Therefore becomes the device doubled and complicated, which increases the manufacturing costs for the device. Therefore the manufacture of the industrial dual-purpose device is considerable limited.

The publication US 4,363,245 discloses a liquid sampling device in which a plurality of sample containers are arranged in a generally spiral pattern for successive passage through a sample section. A sample tube successively removes a small amount of liquid from each container.

Summary the invention

An object of the present invention is a reaction device to create that for an automatic analysis with a high measuring accuracy at a small size without those mentioned above Problems.

Another task of the present Invention is to provide a reaction device that is automatic Immunoassay is suitable.

Another task of the present Invention is to provide a reaction device that is automatic Analysis using an immunoassay is appropriate and for simultaneous execution Reactions of various protocols, such as a one-step procedure and a two-step process without complicated design of the device structure with a high treatment efficiency useful is. This task is explained in more detail below. It is necessary, in some cases the Change response time for example 20 minutes, 40 minutes and 60 minutes. At a certain one-step procedures In an enzyme immunoassay, the protocol has the following steps: reaction, B / F separation (Washing), substrate distribution and fluorescence measurement, whereas with a certain two-step procedure the protocol is different and has the following steps: a first reaction, B / F separation, a second reagent distribution, a second reaction, B / F separation, Substrate distribution and fluorescence measurement. With a system for linear conveying of reaction vessels the washing mechanism or the detection device at the position arranged at which the reaction is completed, or the reaction vessels to another unit from the position where the reaction is accomplished to perform washing or grasping, thereby the number of units increases. The conveyor speed can be used to measure different reaction times changed become. However, if the conveyor speed is decreased to match the long response time, the number of measurements per unit of time becomes smaller. A simultaneous Measure reactions of different reaction times or different ones Logs cannot be run without using many reaction lanes. An automatic analysis system is therefore sought, such Solves problems.

Another task of the present The invention is to create an automatic analysis system that a reaction device with a small size as a whole with a small installation area having.

The reaction device for automatic analysis and in particular a biological sample of the present invention has a conveyor mechanism or transport mechanism to a lens substance and in particular vessels or containers containing a biological sample to promote a center of rotation: where the transport mechanism is a first guide device for guiding containers or Along vessels a spiral path provided in a first horizontal plane and a second guide device to lead of containers or along vessels radial tracks provided in a second horizontal plane; the first guide and the second guide device are arranged concentrically and at different heights; in which the vessels at intersections the spiral track and the radial tracks are arranged to allow horizontal movement to control the vessels; taking the vessels through a rotation of either the first or the second guide means relative to the other guide be transported or transported around the center of rotation.

The radial tracks of the second guide device are common in a radial manner in multiplicity at constant angular intervals intended. The radial path is usually in the form of a Slot that perforates a disc or the like, however, can be a groove.

Summary of the drawings

1 shows a plan view in a schematic manner on the device of the first embodiment of the present invention.

2 shows a vertical sectional view of the apparatus of the first embodiment of the present invention.

3 shows schematically an example of an automatic analysis system which has the reaction device of the first embodiment of the present invention.

4 shows a plan view in a schematic manner on the device of the second embodiment of the present invention.

5 shows a vertical. Sectional view of the device of the second embodiment of the present invention.

6 shows schematically an example of an automatic analysis system which has the reaction device of the second embodiment of the present invention.

7 shows the movement of the reaction vessel during a transfer from a slot to a vessel holding hole.

8A shows a top view and 8B shows a vertical sectional view, wherein the device of a third embodiment of the present invention is shown schematically.

9A shows a top view and 9B shows a vertical sectional view, wherein the device of a fourth embodiment of the present invention is shown schematically.

10 shows schematically an example of an automatic analysis system which has the reaction device of a fifth embodiment of the present invention.

11 shows a movement of a reaction vessel in the device of FIG 10 with a one-step treatment in 40 minutes.

12 shows a movement of a reaction vessel in the device of FIG 10 with a one-step treatment in 20 minutes.

13 shows a movement of a reaction vessel in the device of FIG 10 with a two-step treatment in 20 minutes.

14 shows the movement of the vessel of 13 ,

Detailed description of the preferred embodiments

Due to the above-mentioned structure of the equipment is going along the reaction vessel the radial path of the second guide device promoted if the first leader is rotated while along the reaction vessel the spiral path of the first guide device is promoted if the second guidance facility is rotated. The reaction vessel can be closed any desired Position promoted be by both leadership bodies be rotated. In particular, in the spiral conveyor system all reaction vessels along on the same route (i.e. the spiral train), while the reaction on the the respective vessels. Furthermore, in the spiral system, the vessels are rotated through the rotating plate (i.e. H. the rotary table with radial tracks) as the second guide device driven. Therefore, the requirement for a small design of the equipment met in an advantageous manner by placing a number of reaction vessels on the same lane, the is provided in a variety of lines (a spiral path) in are transported in a narrow radial area.

The first guide and the second guide means are generally made of a circular flat base or one Disc built up. For example, the first guide device a fixed base or a rotating plate that is arranged horizontally is to be with a continuous spiral path that is a spiral groove or can be a spiral perforation hole or a slot. In general is the length the spiral track preferably two or more laps. Moved with the spiral conveyor system the vessel inside or outside by a spiral distance (division) by rotating the second Guide device.

With the above-mentioned structure the expression "means first management facility and the second guidance facility are at different heights or stages arranged to each other “that two guide devices are arranged so that they do not interfere with the rotation of the rotating plate, for example with a suitable space at the top and bottom Height, being a of the devices is arranged at the upper height. Furthermore can the first guide or the second guide device can be provided in a variety of different heights. For example can the first guide device above and below the second guide device for example with a structure made of (spiral path) / (radial path) / (spiral path) be provided or alternatively, the second guide device above and below the first guide device provided with a structure of (radial path) / (spiral path) / (radial path) his. By fixing or synchronously rotating both of the many the same Guide means which are provided above and below, the game of the The point of intersection of the vascular held vessel can be effectively reduced.

In a preferred construction (according to the information of claims three and five) is the first management facility provided as a fixed base or a fixed disc, the or the a spiral track for receiving the bottom portions of the Reaction vessels and To lead the vessels spiral has and can be temperature controllable if necessary is; and the second guide device, which have a plurality of slits separately in the radial direction is rotatable about the axis of rotation above the fixed base provided, which is positioned at the center of the spiral track.

For example, in a vascular delivery mechanism the rotation of the rotating plate for conveying of the reaction vessels controlled are controlled by a rotary drive control device which has a rotary mechanism such as a stepper motor and a servo motor and one Has control mechanism, the reaction vessels at the intersections the spiral track and the radial tracks are held; and being the Reaction tubes spiral are conveyed by the rotary drive control device. Usually the rotary drive is executed in an interrupted manner for insertion and Remove the vessels.

In the construction where the turntable is lower is arranged, the rotary plate is preferably temperature controllable, around the temperature of the liquid to control at the bottom of the reaction vessel. For the Temperature control of the fixed base or the rotating plate is an electric heater useful, the invention not limited to that is. The temperature control of the turntable can be done using a sliding connection device or rotary connection device for Delivering electrical energy or temperature control signals to be executed.

If with the spiral conveyor system the secondary guidance device a turntable for leading applies and arranged above the first guide device the radial path can be a perforation hole (slot); and if the rotary plate is arranged below the first guide device the radial path can either be a perforation hole or a radial groove with a bottom. Similarly, if the first management facility is a fixed base or a fixed washer and above the second guide is arranged, the web to be a perforation hole (slot); and if the fixed base or the washer below the second guide means is arranged, the web can either be a perforation or be a radial groove with a bottom.

The reaction device for automatic analysis the present invention can be highly automated, by an insertion device for an insertion of the Reaction tubes at the intersections the spiral track and the radial tracks at prescribed radial positions and rotational positions and removal means for taking out the imported Reaction vessels from that Intersection at another prescribed radial position and rotational position is provided. If the device with the reaction vessels for different Measuring points is operated simultaneously, for example different ones Reaction time spans (e.g. 20 minutes, 40 minutes and 60 Minutes) or various protocols such as one-step immune response and a two-step immune response, it is desirable that the one introducer or operate a remover at a variety of positions can. This allows the reaction vessels for the one-step immune reaction and for the Two-step immune response can be treated simultaneously. In one such a case is preferably the insertion device or the removal device constructed such that they are rectilinear along the diameter line moves that over the center of rotation of the turntable occurs between a predetermined Gefäßeinführposition and a predetermined vessel removal position (as listed in claim 21 is). This can create a vertical movement mechanism or a vessel holding mechanism (or a vascular suction mechanism) to the vascular insertion position or the vascular removal position be moved. For this purpose the turntable is controlled to intermittently rotating in one direction and it can preferably be controlled so that it turns back or at an angle of rotation turns, which is different from the normal interrupted driving if this is necessary.

The reaction device (incubator) with the above mentioned Vessel conveying mechanism can with a sample distribution device for distributing the sample into the reaction vessel or one Reagent distribution device for distributing a reagent be combined into this in the previous step before that Vessel to that Vessel conveying mechanism introduced becomes. The device can also with a detector, a substrate distribution mechanism, a washing mechanism or the like are combined in the subsequent step, after the vessel from the Vessel conveying mechanism has been removed. Such facilities and mechanisms for the previous and subsequent steps can be independent of the vascular delivery mechanism be provided or they can using the vascular delivery mechanism be provided.

For example (as in claim 11 listed is) on a radially inner or outer side of the radial track that of the higher Arranged in height Turntable a variety of tube holders be provided concentrically; the reaction vessels after the reaction to be introduced into this can; and being connections for one Detector, a substrate distribution mechanism, a washing mechanism or the like on the circulation path outside the periphery of the turntable can be provided. The structure of the vessel holder can be from a vertical perforation hole or a recess exist, but is not particularly limited to, wherein the prerequisite is that he can keep the vessel stable.

The vessel holders can be provided on a circular circumference of the turntable (usually on and along the circumference of the disk), which forms the second guide device independently of the spiral path, and the connections for a detector, a substrate distribution mechanism, a washer Mechanism and the like can be provided on the rotating path. This enables the above-mentioned treatments to be carried out on the turntable. Thus, the vascular delivery mechanism can be used as the delivery device for the required treatment after or during the incubation in the reaction device. As a result, the automatic analysis system can be made small and its mechanism can be simplified in an advantageous manner. In the case where measurements with different reaction time lengths, as mentioned above, are to be carried out simultaneously or if measurements of different protocols, such as a one-step method and a two-step method, are to be carried out simultaneously on the reaction device, the treatments ( Washing, substrate distribution, detection, and the like) for the separate reaction vessels which are taken out of the same slot, can sometimes be carried out simultaneously. In order to provide such simultaneous treatment, the vessel holders are preferably provided in a number of (number of slits) × n, where n is an integer, and when two vessels which are taken out of the same slit are to be treated at the same time the integer n is equal to the value 2. More specifically, the vessel holders have a first group of vessel holding racks provided on the radially outer side of each radial track and a second group of vessel holders each spaced between the racks of the first group are provided. A rack of the first group and a rack of the second group are provided for each of the radial tracks to accommodate the vessels. In this case, for example, the vessel holders of the first group can be used for a treatment that takes a long time, and the vessel holders of the second group can be used for the treatment that takes a shorter time, but the structure of the holding racks is not limited to this.

The content in the reaction vessel can be non-contact can be stirred in the present invention by a magnetic body in arranged the reaction vessel is provided and a magnetic drive device outside the vessel becomes. A preferred magnetic device is a stirring plate with magnets that are arranged along the spiral path and that are driven back and forth in the direction of rotation of the disc. The reciprocating movement of the stirring plate in approximately the spiral direction can be effected by the stir plate back and forth at a certain angle around the center of rotation of the guide element is moved. For magnetic stirring the reaction vessel is preferred designed from a non-magnetic material, and the fixed Base and at least the table arranged under the rotating plate designed non-magnetic.

In a preferred construction of the Automatic analysis system using the reaction device described above (as listed in claim 21 ), a sample holder can be placed below, above or at the height of the reaction device Carrying an analysis sample containing arranged in a circle containers or a distributor for distributing a prescribed amount the samples are provided to the reaction vessel his. Another preferred construction can be below, above or in height of the reaction device a reaction vessel supply holder with the to the conveyor mechanism in a matrix or on subjects reaction vessels to be supplied and a delivery device for delivering the sample container from the reaction vessel supply holder to the funding mechanism in the reaction device be provided. In such a way, the installation area of the Automatic analysis system significantly reduced by making the room three-dimensional is being used.

If with the above-mentioned structure for example with a spiral conveyor system the reaction vessels adding the sample and the reagent at the intersection of the innermost or extreme Section of the spiral path and the radial paths are set the reaction vessels on one Transported by train, which is the sum of the rotational movement (spiral movement) and the Radial movement of the reaction vessels results with which all Reaction vessels on the like Train can be transported effectively in a small space.

If the length of the spiral track is two laps or more (720 ° or more) and if the turntable at a rate of 20 minutes per revolution is rotated, then need two turning cycles 40 minutes, and different reaction times can optionally be given to the respective reaction vessel by simply the radial position (time) for the removal of the vessel is changed. In in this case the device be constructed such that the reaction vessels at the same angular position can be removed, making a removal device sufficient which has a linear scanning mechanism and is relative is simple. As described above, the Response times for the respective reaction vessel varies by changing the distance of the reaction vessel. Alternatively, the reaction time can also be varied by the Translucent guide positions the reaction vessels are changed, the distance positions remain unchanged.

In yet another example, vessel holders are arranged outside the radial paths (slots) of the rotary plate to keep the reaction vessels concentric with the rotary plate, and a washing mechanism, a detector or the like are provided on the circulation path of the vessel holders; and the reaction vessels become full end of the reaction transferred to the vessel holders. This enables the washing treatment and the detection treatment to be carried out on the same vascular conveying mechanism, thereby simplifying the whole unit.

Furthermore, in one embodiment, in which the reaction vessels for different Protocols such as a one-step procedure and a two-step procedure simultaneously in the same device arranged, with intermediate washing in the two-step process accomplished by washing the reaction tube to a vessel holder brought to the second group, the washing is done there and the vessel to the original Radial orbit (slot) returned. This allows the vessel holders the first group for End-of-wash treatments for both the one-step process as well as the two-step process without any difficulties be applied. If vessels with different Response measurement time are arranged in the same device, the Treated vessels be by the vessel holder the second group. Treating The various measurement points mentioned here include a measurement through different protocols, a measurement at different times, a measurement through different protocols at different times etc.

The reaction device of the present invention can be used as an automatic analysis system for recording or measuring a lens substance by applying a reaction in a prescribed time is effected. The captured or measured The object can be any of the lens substance itself, a labeled compound (for example a fluorescent substance), which is derived by marking the lens substance, and a Substance that is generated by the labeled compound (for example a fluorescent substance produced by a labeled enzyme becomes). The reaction in the reaction device is not particularly limited, however the device is especially for Suitable immune reactions. Typically, the reaction can be a one step process or a two-step process using an enzyme as the marker, an antibody to the biological Objective substance is marked by the enzyme and then this a solid surface is deposited to form a complex.

five Embodiments, which illustrate the present invention are as follows described.

Embodiment 1

1 shows a plan view of a reaction device (incubator) of this embodiment. 2 shows a sectional view taken along a line AA in 1 ,

In the drawings the fixed plate has 1 a shape of a horizontal disc as the above-mentioned first guide means and it is through the lower support plate 10 together with a sheet-shaped heating device 7 fixed and supported, which is provided on the entire lower surface of it. A temperature sensor 11 is provided on the side surface of the fixed plate to the temperature of the fixed plate 1 by a temperature control device 40 to monitor and control. On the top surface of the fixed plate 1 is a continuous spiral groove (spiral path) 2 provided that has a spiral shape and a width that is slightly larger than a reaction vessel 5 is. The spiral groove 2 has a length of approximately two rounds (720 °) in this embodiment.

Above the fixed plate 1 is a turntable 3 as the second guide means provided to be horizontal relative to the fixed plate 1 is rotatable. On this turntable 3 are twenty slots (radial orbits) 4 formed, which extend separately from the center in a radial direction at a constant radial angle with a width that is slightly larger than the size of the reaction vessels.

An axis body or a shaft 6 at the center of the turntable 3 is through a camp 13 supported and the rotation of the motor 16 becomes the turntable 3 through the gear 12 transferred that to the axle beam 6 is provided. A stepper motor is called the motor 16 applied to easily control with the angle of rotation. The engine is controlled by an engine control device 41 controlled so that it moves intermittently to stop at a prescribed angle of rotation.

In this embodiment, a non-contact stirring mechanism is provided by using magnets to shorten the reaction time and make the reaction smooth. More specifically, the fixed plate is 1 made of a non-magnetic material and under the fixed plate 1 is a stir plate 8th provided that has an annular plate shape and magnets 9 has that along the spiral groove 2 are arranged. A cam 14 with the drive shaft of a shaker motor 15 is loosely attached to an elongated hole 24a a shaking arm 24 on the stir plate 8th is appropriate. The stir plate 8th becomes rotating and reciprocating through a certain angle by the rotation of the cam 14 emotional. The device having the structure described above moves magnetic particles (not shown in the drawings) into the reaction vessel 5 have been added back and forth according to the reciprocating movement of the stirring plate 8th , with which the liquid contained in the sample and the reactant are stirred in order to allow the reaction to proceed efficiently. The magnets 9 are preferably under the reaction vessels 5 arranged. The magnets of this embodiment are located under the spiral.

In the structure of this embodiment described above, a reaction vessel 5 that to position P ₁ at the intersection of the spiral 2 and the radial slot 4 according to 1 is inserted slowly with the rotation of the rotating plate in a spiral radially outside along the slot 4 promoted. If the turntable 3 has been rotated through 360 °, the reaction vessel reaches 5 the position P ₂ in 1 , and if the turntable 3 has rotated further by 720 °, the reaction vessel reaches 5 the position P ₃ according 1 ,

Accordingly, the reaction vessels successively supplied to the position P _{1 are} constantly conveyed along the spiral conveying path for a predetermined time, whereby the incubation is carried out at a constant temperature caused by the fixed plate 1 controlled by a heater 7 is held.

With the reference symbol 17 is an insertion-removal mechanism for inserting the reaction vessels 5 in the aforementioned vascular delivery mechanism and for removing them from the mechanism. In this embodiment, a suction pad support 23 with a suction pad 23a for lifting the reaction vessel 5 controlled to move horizontally and vertically to insert and remove the reaction vessel at positions inside and outside of the vessel delivery mechanism. More specifically, a horizontal feed mechanism is made of a horizontal feed screw 19 by a stepper motor 18 is driven, and a guide shaft 20a formed and a vertical feed mechanism is from a vertical feed screw 22 by a stepper motor 21 is driven, and a guide shaft 20b educated. The feed mechanism controls the horizontal and vertical movement of the suction pad support 23 ,

3 schematically shows an automatic analysis system with the above-described reaction device (incubator) 33 with reference to the 1 and 2 ,

At the in 3 shown plant holds a reaction vessel supply holder 26 a turntable type reaction vessel in which a magnetic body is contained. The reaction vessels 5 are individually from the reaction vessel supply holder 26 taken out to a delivery sled 28 through a vascular transmission mechanism 29 transferred (the detailed description is omitted here). This vascular transfer mechanism can be of the same type as the insert-remove mechanism mentioned above 17 his. The delivery mechanism for the vessels, which is selected according to the measurement points, to the vessel holders on the circumference of the reaction vessel supply holder 26 is not explained here since this is not an essential object of the present invention. However, this mechanism is designed in such a way that the vessels for the intended measuring points are delivered in succession.

Then in this embodiment the delivery carriage 28 of the delivery carriage mechanism 27 once in front of the sample holder 30 the turntable stopped the sample container 31 holds. The sample is taken from the sample container 31 to the reaction vessel 5 on the delivery sled 28 by a known suitable distribution mechanism 32 distributed.

The sample vessel 5 that has received the distributed sample is sent through the delivery sled 28 delivered and stops at position P ₄ . There is the sample vessel 5 as a reaction vessel 5 to an intersection P _{1 of} the innermost round of the spiral groove 2 and a slot 4 by means of the insertion-removal mechanism mentioned above 17 introduced.

At the reaction device (incubator) 33 , the turntable 3 controlled to move in a counterclockwise direction 3 in an interrupted manner by an angular distance between the slots 4 spins at every minute. There are 20 slots and thus the rotating plate is rotated in one cycle (360 °) in 20 minutes, causing the vessel to move outward (or inward) by a spiral line spacing. As a result, the vessel after the reaction of 20 minutes and the vessel after the reaction of 40 minutes each reach positions P ₂ and P ₃ in the same radial direction (line AA in FIG 1 ).

The reaction vessel 5 after a response of a prescribed period of time, in this embodiment, by the insert-remove mechanism 17 to a turntable 35 transferred with a cleaning mechanism (washing mechanism) 50 , a substrate distribution mechanism 51 and a captor 52 is equipped, and is treated for detection by the detector. The reaction vessel 5 after detection, it becomes a discharge hole 34 through the same import-remove mechanism 17 issued.

The treatment speeds of the washing mechanism, the substrate distribution mechanism and the detector are set depending on the incubation treatment speed. If the samples have different reaction times such as one from the 20 minute position P ₂ (removal process C in 3 ) removed sample and another from the 40-minute position P ₃ (removal process B in 3 ) If the removed sample is treated according to the measuring points, the samples can be treated without reducing the treatment performance of the incubator by increasing the treatment speed per unit of time twice as fast as that of the incubator.

Embodiment 2

The 4 to 6 show an example of a reaction device 133 , with the vessel holding holes (vessel holder) 200a . 200b for reaction vessels 5 cyclically on the periphery of a turntable 103 are provided to the rotary plate 3 of 1 of the embodiment 1 is equivalent. Corresponding to this is a strip of a circular groove 104 provided the height of the reaction vessels 5 to evenly shape that on the spiral groove 2 on a fixed plate 101 are mounted. The structure is the same with respect to the other points as that in the 1 to 3 shown device, so the same reference numerals as in the 1 to 3 find use without explanation. The vessel holding holes 200a . 200b are on the turntable 103 dimensioned such that the vessels 5 can be held through the hole without play.

In this embodiment, the vessel holding holes are 200a . 200b on the circumference of the rotating plate 103 intended; being the washing mechanism 50 , the substrate distribution mechanism 51 and the capturer 52 successively along the path of movement of the vessel holding holes 200a . 200b are arranged like this in 4 is shown; and wherein the detection treatment for the reaction _vessel supplied to the P _OUT position by the rotation of the rotating plate 103 is performed.

6 shows schematically the entire automatic analysis system, the reaction device 103 with the in 5 structure shown. This automatic device differs from that of 3 in that the vessel holding holes 200a . 200b for holding the reaction vessels 5 on the circumference of the rotating plates 103 are provided and the washing mechanism 50 , the substrate distribution mechanism 51 and the capturer 52 along the delivery path of the vessel holding holes 200a . 200b are provided, whereby the turntable 35 becomes unnecessary.

This embodiment shows an apparatus capable of taking measurements for points that require different response times (e.g. 20 minutes and 40 minutes). This device has twenty slots 4 and forty vessel holding holes 200a . 200b , which is twice the number of slots 4 corresponds, at a constant distance at the positions radially outside of the slots, and the rotating plate 103 is rotated intermittently by a distance (1/40 rotation cycle, ie by 9 °), whereby 20 minutes are required for one rotation.

In the case where the measuring point comprises a 20-minute measurement and a 40-minute measurement, two reaction vessels are used 5 . 5 , in which the reaction is completed, brought to positions P ₁ and P ₃ , respectively. A first reaction vessel (at position P ₃ after the 40 minute treatment) becomes a vessel holding hole 200a transferred at position P _out (process D for the 6 and 7 ). Then another reaction vessel (at position P ₂ after the 20 minute treatment) becomes a vessel holding hole 200b at position P _out (process E in the 6 and 7 ) radially outside of the slot 104 and between the two vessel holding holes 200a transfer. The transferred reaction vessels 5 become positions below a washing mechanism 50 , a substrate distribution mechanism 51 and a captor 52 delivered to be treated sequentially. The reaction vessels 5 become a waste container after the measurement 34 after approximately one turn of the rotating plate (operation F in 7 ).

Since in the construction set out above, the rotary plate 103 for a 20-minute cycle or a 0.5-minute interval, the measuring system is set up so that the steps of sample distribution, washing and acquisition are each completed within 0.5 minutes.

Due to the structure set out above, the separate turntable 35 for washing, substrate spreading and detection can be omitted to effectively make the automatic analysis system (particularly the automatic immunoassay system) using the reaction apparatus small.

For the purpose of a further small design, the sample holder 30 forming rotary table or under the reaction device 133 arranged to use the space three-dimensionally to reduce the area occupied by the device. The type of tube holder 26 is not limited to the rotary table type, but can be of a compartment type that has compartments according to the number of measuring point numbers.

Embodiment 3

This in the 8A and 8B The exemplary embodiment shown is characteristic in comparison to exemplary embodiment 1 in that the fixed plate 1 than the first guide device according to the 1 and 2 to a fixed disc 201 has been changed to a vertically perforated spiral track 202 Has; being the bottoms of the reaction vessels 5 at the intersection of the slots 4 than the radial paths of the second guide means and the spiral path described above 202 on the upper surface of a flat fixed disc 240 can slide that with an electric heater 7 is equipped on the back.

The structure is the same with respect to the remaining parts as that in the 1 and 2 The structure shown and the same reference numerals are used without explanation in order to simplify the description.

In the construction of this embodiment, the spiral track 202 a vertical perforation hole and has no groove structure, whereby it is easy to clean and no difficulty caused by a foreign substance entering the groove during delivery of the vessel in an advantageous manner.

Embodiment 4

This in the 9A and 9B The exemplary embodiment shown is characteristic in comparison to exemplary embodiment 1 in that the fixed plate 1 than the first guide device according to the 1 and 2 to a fixed disc 301 has been changed to a vertically perforated spiral track 302 has and above the turntable 3 with slits 4 is arranged; being the bottoms of the reaction vessels 5 at the intersection of the slots 4 than the radial paths of the second guide means and the spiral path mentioned above 302 on an upper surface of a flat fixed disc 340 can slide that with an electric heater 7 is equipped on the back. In this construction, a device can be provided that rotates the fixed disc 301 , which is arranged above, prevented if necessary.

The structure is the same with respect to the remaining parts as in the 1 and 2 and the same reference numerals are used without explanation to simplify the description.

In the construction of this embodiment the same effect as in embodiment 3 can be achieved.

Embodiment 5

The 10 to 14 show a preferred construction and operation of an automatic analysis system for an enzymatic immunoassay. The system uses a reaction device that has the same structure as that of 2 has and vessel holding holes 200a . 200b at the sections radially outside of the slot on the turntable.

In this embodiment, a delivery mechanism is a fixed disc 201 (please refer 8th ) with a vertically perforated spiral track and a turntable 203 formed, which is arranged above this and twenty slots 204 than the radial orbits. On the radially outer side of the slots 204 on the turntable 203 are a first group of vascular holding holes 200a on the extension lines of the slits and a second group of the vessel holding holes 200b between the vessel holding holes 200a the first group. The hub 203 turns in an interrupted manner by a distance in principle (18 ° in this embodiment) clockwise, as shown by the arrow in the drawing. This causes the reaction vessels to run 5 , which are introduced at the intersections of the spiral path and the slots to move to the next outer path of the spiral by a rotation cycle of the disc. Such a structure and such a delivery process are the same as in Embodiment 2, referring to FIG 4 to 6 is described above.

In this embodiment there are twenty slots 204 than the radial orbits and the spiral orbital is provided in approximately four rounds (1440 °) with some excess length (e.g. an excess length for a rotation of 180 ° at the start or end point of the rotation of 1440 °). The hub 203 can rotate intermittently to complete a turning cycle in 10 minutes.

Line XX in the drawings shows the scan line of the vascular insertion removal mechanism 210 that is provided to run along a rail 211 to move on the diameter line of the turntable. In a reaction vessel 5 a reactant is added and a lens sample is on a sample distribution track 212 distributed (the distribution device is not shown in the drawing). Then the reaction vessel 5 pulled up at the position So by a lifter (not shown in the drawing) of a gripping type provided at the lower position of a head of a vessel insertion-removing mechanism. The head is moved along the line XX to a position above the import position S ₁ . There the reaction vessel 5 lowered and to the intersection of the spiral path and the slot 204 introduced. This process is carried out every time the turntable 204 rotated by one unit (18 °) in an interrupted manner. This makes twenty reaction vessels 5 Delivered in one round and eighty reaction tubes are delivered in four rounds in a continuous manner.

The reaction vessel 5 for a 40 minute step, the turntable is conveyed to a position S ₅ by four turning cycles and is taken out (raised) along line XX to a position S ₆ by the import-remove mechanism 210 moved and into a vessel holding hole 200 introduced (see 11 ). The reaction vessel 5 for a 20 minute step, S ₃ is taken out at the two-round position in the same manner and is put into the vessel holding hole 200b introduced when the hole 200b has reached position S ₆ by the turntable 203 has been rotated half a distance, ie 9 ° (see 12 ).

Through the above-described operations, the reaction vessels become the vessel holding holes 200a . 200b that are cyclical along the circumference of the turntable 203 are provided, promoted and are treatments for washing 50 , a substrate distribution 51 and a grasp 52 by the mechanisms that are arranged along the circulation route of the vessel holding holes that coincide with the turntable 203 move. Then the reaction vessels are conveyed to a position S ₅ or S ₆ by the rotation of the disk by the vessel insertion-removal mechanism 210 removed (raised) and to the cup dispenser 34 issued.

In the case where the reaction vessels with different reaction times are arranged on the disk at the same time, as is shown in FIGS 11 and 12 is shown, the respective reaction vessels are treated by the vessel holding holes 200a the first group for a 40 minute response and those 200b the second group can be used for a 20 minute reaction.

On the other hand, in two 40 minute step reactions, the reaction vessel 5 when it has been conveyed to the two-round position S ₂ in the same manner as described above, the turntable 203 rotated by half a unit and the reaction vessel is inserted into the vessel holding hole 200b introduced, which has reached position S ₆ ; a washing treatment is carried out and a second reactant is distributed (55); returns the reaction vessel 5 from position S ₆ to position S ₃ in the slot or the disc continues to rotate in the normal direction of rotation after the distribution of the second reactant; and the reaction vessel returns from position S ₇ to position S ₈ . Thereafter, the treatment is carried out in the same manner as the 40-minute step treatment mentioned above.

11 shows the process of only a 40 minute step treatment by moving the reaction vessel. The reaction vessel introduced to position S ₁ is conveyed to position S ₅ by four rotations of the disc. At this point, the reaction vessel becomes the vessel holding hole 200a (or to the vessel holding hole 200b ) at position S ₆ . The treatments of washing, substrate distribution and detection are carried out there.

12 shows the process of just a 20 minute step treatment by moving the reaction vessel. The reaction vessel introduced to position S ₁ is conveyed to position S ₃ by four rotations of the disc. At this point, the reaction vessel becomes the vessel holding hole 200a (or to the vessel holding hole 200b ) transfer. The treatments of washing, substrate distribution and detection are carried out there.

Incidentally, to practice a 10-minute step treatment, the reaction vessel at position S _{2 is taken out} by rotating the disk and becomes the vessel holding hole 200a (or 200b ) transfer.

13 shows the process of just a two 40 minute step treatment by moving the reaction vessel. The 14A to 14D additionally show the details of it. The reaction vessel introduced at position S ₁ is conveyed to position S ₃ by two rotations of the disc. At this point, the reaction vessel is removed from the slot (see 14A ) Then the turntable 203 rotated half a distance or ½ division (in the normal direction) around the vessel holding hole 200b to position S ₆ and the reaction vessel is placed in the vessel holding hole 200b introduced (see 14B ). Then washing (intermediate washing) and the distribution of the second reactant ( 55 ) executed. The treatments mentioned above are common in 14C shown.

Immediately after the second reaction medium has been distributed to the reaction vessel, the turntable becomes 203 rotated in the reverse direction and the reaction vessel returns to position S ₃ in the slot by the turntable 203 is further rotated half a distance (division). The vascular return process is reversed to the process described with reference to FIG 14A to 14C is explained. The vascular return process is common in 14D shown. The reaction vessel, which has returned to the slot, is immediately conveyed to the starting position (the reversing start point after the distribution of the second reactant). Instead, after distributing the second reactant, the reaction vessel can go to position S ₈ in the slot 204 return to the point at which the reaction vessel has been moved to position S ₇ by normal rotation of the disc. Otherwise, the turntable is quickly rotated in the normal direction to bring the reaction vessel to position S ₇ with the reaction vessel returning to position S ₈ in the slot, and then the turntable is rotated in the reverse direction to the home position. When a rectilinear vascular insertion-removing mechanism as in this embodiment is used in these operations, the rotation of the turntable is not controlled by an interrupted one-distance control (one-division control) but by a half distance (normal rotation and reverse rotation) or controlled by several distances (divisions) for quickly moving the vessel to the opposite position because of the vessel holding holes 200b are each offset by half a distance or division from the slots.

If the reaction vessel that goes to the slot 204 has returned to position S ₅ after a total of four rounds, it becomes the vessel holding hole 200a is transferred at position S ₆ and the treatment of washing (final washing) is subjected to substrate distribution and detection. As described above, after the intermediate washing and dispensing of the second reactant, the reaction vessel may return from position S ₆ to position S ₃ by rotating the disc backward, or from position S ₇ to S ₈ by one thereon return the following approximately half a turn of the disk in the normal direction of rotation. Otherwise, it can return from position S ₆ to position S ₄ by a subsequent interrupted approximately one rotation in the normal direction of rotation. For these processes, the device can be equipped so that the turntable 203 turns quickly in the normal direction or in the reverse direction. For normal rotation and backward rotation of the turntable, the above-mentioned spiral path excess is effective at the start point or the end point.

The one-step treatment and the two-step treatment described with reference to the 11 to 13 can be carried out in combination. A 20-minute step treatment and another 40-minute step treatment can be performed in combination by the treatment processes of the 11 and 12 can be controlled for the respective reaction vessels by means of a microprocessor unit. A one-step treatment and a two-step treatment can be performed in combination by the treatment processes of 11 and from 13 , of 12 and 13 or from 12 and 13 can be controlled for the respective reaction vessels by control by means of a microprocessor unit. In this process, the turntable 203 be rotated in the reverse direction if necessary.

The reaction vessel of the present invention Fulfills at the same time the requirements for an effective measurement process a reaction in a short time with high accuracy without position difference such as a temperature distribution by all Reaction vessels through transported the same train and the requirement for a small design of the device.

According to the invention, vessels for measuring points can be different Response times can be treated effectively mixed, without the treatment efficiency to reduce.

When the present invention is based on an automatic analysis system is used that has an immune response uses, can Reaction vessels for different Treatments such as a one-step treatment that no intermediate washing required, and a two-step treatment, which requires intermediate washing with the same reaction device without any Inconvenience.

The reaction device, with the reaction vessels in one Rotary table introduced and removed from it by a vascular insertion removal mechanism, that moves in a straight line can be smaller in size be designed and simplified in terms of mechanism are due to the simple structure of the drive mechanism, and the production cost of the device are reduced, which has significant effects on industrial Application result.

The automatic analysis system can be further simplified be by the vessel holder for the reaction vessels the reaction is arranged along the circumference of the rotating plate, because the funding mechanism for the Response can also serve to detect the lens substance.

The device using the immune response can continue be simplified by adding the vessel holder for the reaction vessels the reaction is arranged along the circumference of the rotating plate, because of the treatments of intermediate washing and final washing one and the same washing device can be carried out.

Through those described above Overall, the present invention creates the device with one simple mechanism, high accuracy and high performance at low cost.

Claims (21)

Reaction device ( 33 ) for an automatic analysis with. a transport mechanism for transporting containers ( 5 ) containing a substance to be analyzed around a center of rotation; the transport mechanism comprising a first guide device ( 1 ) for guiding containers along a spiral path formed in a first horizontal plane ( 2 ) having; characterized in that the transport mechanism further comprises a second guide device ( 3 ) for guiding the containers along radial paths formed in a second horizontal plane ( 4 ) having; wherein the first guide device and the second guide device are arranged concentrically and at different heights; the containers ( 5 ) at intersections between the spiral path ( 2 ) and the radial orbits ( 4 ) are arranged to control the horizontal movement of the containers; the containers being transported around the center of rotation by a rotary movement of the first or the second guide device with respect to the other guide device. Apparatus according to claim 1, wherein the second guide means a plurality of radial tracks arranged at constant angular intervals ( 4 ) having. Apparatus according to claim 1 or 2, wherein the first guide means immobile and the second guide device is rotatable, the second guide device above the first management facility is arranged. Device according to one of claims 1 to 3, wherein the second guide means immovable and the first guide device is rotatable, the first guide device being arranged above the second guide device. Apparatus according to claim 3 or 4, wherein a temperature-controlled heating device ( 7 ) to regulate the surface temperature of the stationary guide device ( 1 ) provided. Device according to one of claims 1 to 5, wherein the first guide means or the second guide device in a double embodiment spaced one above the other are arranged and the other guide device is arranged in between, and wherein the corresponding tracks the double embodiment provided management facility are arranged aligned relative to each other. Device according to one of claims 1 to 6, wherein both guide devices ( 201 . 3 ) a train or trains ( 202 . 4 ) in the form of vertical perforation holes; a support surface under the guide device ( 240 ) is arranged for slidably holding the undersides of the containers, which at the intersections between the spiral path ( 202 ) and the radial tracks in the form of vertical perforation holes ( 4 ) are used; and wherein the temperature controlled device ( 7 ) is suitable for regulating the surface temperature of the mounting surface. Device according to one of claims 1 to 7, wherein the transport mechanism is suitable for a first container type for a prescribed long-term treatment and a second type of container for a prescribed one Short-term treatment at the same admission position or at separate positions Recording positions and is able to use the container for short-term treatment to release at an intermediate point on the transport route. Apparatus according to claim 3 or 4, wherein the rotatable guide means ( 103 ) over the immovable guidance device ( 101 ) is arranged and several container holders ( 200a . 200b ) are arranged on the radially outer or inner side of the radial tracks in a concentric circle on the rotatable guide device. Apparatus according to claim 9, wherein the number of container holders corresponds to n times the number of radial orbits (where n is one is an integer), and the container holder at constant intervals arranged on the circumference of the rotating guide device are. Apparatus according to claim 10, wherein container holder ( 200a ) a first group of container holders on the radially outer and inner side of the radial tracks ( 4 ) are arranged and container holders ( 200b ) a second group of container holders ( 200b ) are arranged between the respective container holders of the first group of container holders; and wherein a set of container holders, each having a holder of the first and second groups, receive containers from the same radial path. Apparatus according to claim 11, wherein the container holder of the first group the containers for one last Pick up the treatment step and the container holder of the second group the containers for one Include intermediate treatment step. Device according to one of claims 9 to 12, wherein the device at least one of the following openings has: a reagent discharge port for dispensing a reagent into the container, a substrate discharge opening for Dispensing a substrate into the container, a washing opening for Wash out the inside of the container and a detection opening for Detecting the substance to be analyzed in the container, wherein the openings along the circular Curve of the container holder are arranged. The device of claim 13, wherein the device comprises two or more or all openings having. Device according to one of claims 1 to 14, wherein the device a container insert and - removal device for inserting or removing a container in or from the intersection between the spiral Path and the radial path or in or from the container holder having. Apparatus according to claim 12, wherein the device comprises a container insertion and removal device for inserting or removing a container in the point of intersection between the spiral path and the radial path Web and into the first group and the second group of container holders or from the first group and the second group of container holders and a control device for controlling the container insertion and - removal device; and where the container insertion and - removal device is able to remove the container from the Intersection to the second container holder to be transported and transported back to the intersection. Apparatus according to claim 15 or 16, wherein the container insertion and removal device between a predetermined container insertion position and the container removal position in a straight line along the diameter line of the device emotional. Device according to one of claims 1 to 17, wherein the device has a magnetic device for moving a magnetic body which is added to the container is, the magnetic device having magnets which are substantially along the spiral Web and are arranged so that they back and forth along the path around the center of rotation move. Device according to one of claims 1 to 18, wherein the device a rotary drive control device for controlling the rotational movement of the has rotating disk for transporting the container. The apparatus of claim 19, wherein the rotary drive control device is able to cause the rotating disc to turn itself to turn in one direction and in the opposite direction. Device according to one of claims 1 to 20, further comprising Means for providing a sample stock that carries many containers that Contain samples to be analyzed, and under the reaction device over which Reaction device or arranged at the same height as the reaction device is.